Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease - Full Text View

Sponsor:	Brigham and Women's Hospital
Collaborator:	National Institutes of Health (NIH)
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00865124

Purpose

Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. This study will test the hypothesis that MR antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function.A randomized, double-blind study will be conducted, in which subjects with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:

spironolactone
hydrochlorothiazide plus potassium
placebo.

Condition	Intervention
Type 2 Diabetes Mellitus Vascular Disease	Drug: Spironolactone Drug: hydrochlorothiazide + potassium Other: placebo

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Official Title:	Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Vascular Diseases

Drug Information available for: Spironolactone Hydrochlorothiazide Potassium chloride

U.S. FDA Resources

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

MR blockade improves coronary circulatory and cardiac diastolic function in individuals with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

MR blockade improves renovascular function in subjects with T2DM [ Time Frame: two and six months ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	September 2008
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental MR blockade (Spironolactone)	Drug: Spironolactone 25 mg daily
2: Active Comparator hydrochlorothiazide + potassium	Drug: hydrochlorothiazide + potassium 12.5 mg hydrochlorothiazide daily plus 10mEq potassium
3: Placebo Comparator placebo capsule	Other: placebo placebo capsule

Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age 18-64 years
type 2 diabetes mellitus
hypertension
healthy volunteers

Exclusion Criteria:

ischemic changes on resting electrocardiogram
clinical evidence of heart disease (angina, heart failure, unstable angina), cerebrovascular or peripheral vascular disease
significant cardiac arrhythmias
aortic stenosis
2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia
bronchospastic lung disease with active wheezing
known hypersensitivity to adenosine
hemoglobin A1C > 8.0%
use of vitamin A, C, E, or antioxidants
GFR < 50 ml/min
serum potassium > 5.0 mmol/L
use of potassium sparing diuretics
current smoker
pregnancy
renal disease not related to diabetes mellitus
uncontrolled hypertension, systolic BP > 160 mmHg and diastolic BP > 100mmHg
use of hormone replacement therapy
other major medical illness. Subjects with evidence of ischemia on the first adenosine-stimulated PET study will be withdrawn from the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00865124

Contacts

Contact: Gail K Adler, MD, PhD	617-732-8742 ext 15899	gadler@partners.org
Contact: Valerie L Curren, BA	617-732-6870	vcurren@partners.org

Locations

United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Gail K Adler, MD, PhD
Sub-Investigator: Rajesh Garg, MD
Sub-Investigator: Raymond Y Kwong, MD
Sub-Investigator: Marcelo F Di Carli, MD
Sub-Investigator: Marie Gerhard-Herman, M.D.

Sponsors and Collaborators

Brigham and Women's Hospital

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Gail K Adler, MD, PhD

Brigham and Women's Hospital

More Information

No publications provided

Responsible Party:	Brigham and Women's Hospital ( Gail K. Adler, MD, PhD )
Study ID Numbers:	2007-P-000564, 1 R01HL 087060-01A2
Study First Received:	March 17, 2009
Last Updated:	September 15, 2009
ClinicalTrials.gov Identifier:	NCT00865124 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Mineralocorticoids
Sodium Chloride Symporter Inhibitors
Diuretics
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Diabetes Mellitus
Vascular Diseases
Endocrine System Diseases
Cardiovascular Agents

Antihypertensive Agents
Hormones
Hydrochlorothiazide
Pharmacologic Actions
Spironolactone
Membrane Transport Modulators
Aldosterone Antagonists
Natriuretic Agents
Therapeutic Uses
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010